P914: VENETOCLAX IN RELAPSE/REFRACTORY AL AMYLOIDOSIS- A MULTICENTER INTERNATIONAL RETROSPECTIVE REAL-WORLD STUDY
Authors: Eyal Lebel, Efstathios Kastritis, Giovanni Palladini, Paolo Milani, Foteini Theodorakakou, Shlomzion Aumann, Noa Lavi, Liat Shargian, Hila Magen, Yael Cohen, Moshe Gatt, Iuliana Vaxman
Journal: HemaSphere (2023)

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: AL amyloidosis (AL) is a characterized by progressive multi-organ damage due to misfolded light chains (LC), secreted by aberrant monoclonal plasma cells. Thus, lowering LC levels to achieve affected organ responses and prolong survival has become the major goal of treatment. As t(11;14) is present in close to 50% of AL cases, venetoclax may become a promising therapy for this disease. Aims: To add our experience of 7 centers from 3 countries with venetoclax in relapsed/refractory AL amyloidosis. Methods: We retrospectively identified all AL amyloidosis patients who received at least one dose of venetoclax outside a clinical trial. Event-free survival (EFS) was defined as the time from the first day of venetoclax administration to hematologic progression or therapy change for inadequate response or death. The duration of response (DOR) was defined as the time from the first day of hematologic response to venetoclax to progression/death, in patients who achieved at least partial response. Results: Twenty-six AL patients from 7 centers, who received venetoclax between March 2019 and October 2022, were identified and included in the study. The median age at venetoclax initiation was 65 years (range 50-88) and 10 patients (38%) were 70 years or older. The median number of organs involved was 2 (range 1-6), and the median number of prior lines of therapy was 3.5 (range 1-7) (Table). Nine patients (35%) received venetoclax monotherapy and 9 (35%) received venetoclax in combination with dexamethasone. Eight patients (31%) received venetoclax in combination with daratumumab, one of them also with bortezomib. The median venetoclax dose was 400 mg/d (range 200-800 mg). The overall response rate (ORR) to venetoclax-based therapy (at least partial hematologic response) was 23/26 (88%). Nine patients (35%) achieved a complete hematologic response (CR), 9 patients (35%) achieved very good partial hematologic response (VGPR), and 5 patients (19%) achieved partial hematologic response (PR). Three patients (12%) had no response (NR). Thus, 18/26 (69%) achieved a depth of response of VGPR or CR. The median DOR was 25 months (95% CI 8-29). Within the subgroup of patients who achieved VGPR/CR, the mDOR was similar at 25 months (95% CI 2-29). Three patients in our cohort didn’t harbor t(11;14). One achieved CR, one PR, and one NR. The median follow-up from initiation of venetoclax therapy was 33 months (95% CI 26-39). At data cutoff 20 patients (77%) were alive. Five patients (19%) died of disease complications and one (4%) died due to infection. The median EFS was 25 m (95% CI 9.7 – not reached). The median OS for the whole cohort was 33 m (95% CI 25.9-39.2). At last follow-up, twenty patients (77%) were still on therapy. The reasons for treatment discontinuation were hematologic PD in 3 patients and toxicity in 3 patients (one due to hematological toxicity and two due to infections). A total of 9 grade 3-5 toxicities were documented in the study, in a total of five patients (19%): three of which were infections, two of grade 3 and one of grade 5, one diarrhea of grade 3, while the others were hematological toxicities. Twelve patients (46%) received antibiotic prophylaxis while on venetoclax. Six patients (23%) had infections, three grade 3-5. Tumor lysis syndrome was not seen in any patient in our cohort. Summary/Conclusion: Our results support previous retrospective reports. Prospective studies with venetoclax in various settings, including earlier in AL course, as well as in various combinations should be encouraged.Keywords: Venetoclax